A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation

Summary

The primary objective of the study was to evaluate the efficacy of lumacaftor in combination with ivacaftor at Week 24 in participants aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.

Timeline

Start

2013-04

Primary completion

2014-04

Completion

2014-04

Outcome

Met primary endpoint

paper In both studies, there were significant improvements in the primary end point in both lumacaftor-ivacaftor dose groups; PMID 25981758 ↗

registry Placebo vs LUM 600 mg qd/IVA 250 mg q12h; p = 0.0004; Least Squares (LS) Mean Difference 2.62 (95% CI 1.18 to 4.06); NCT01807949 ↗

Publications

• Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
• Acaster S, Mukuria C, Rowen D, Brazier JE, Wainwright CE, Quon BS, Duckers J, Quittner AL, Lou Y, Sosnay PR, McGarry LJ. Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised. Value Health. 2023 Apr;26(4):567-578. doi: 10.1016/j.jval.2022.12.002. Epub 2022 Dec 9.
• Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
• Flume PA, Suthoff ED, Kosinski M, Marigowda G, Quittner AL. Measuring recovery in health-related quality of life during and after pulmonary exacerbations in patients with cystic fibrosis. J Cyst Fibros. 2019 Sep;18(5):737-742. doi: 10.1016/j.jcf.2018.12.004. Epub 2018 Dec 23.
• McColley SA, Konstan MW, Ramsey BW, Stuart Elborn J, Boyle MP, Wainwright CE, Waltz D, Vera-Llonch M, Marigowda G, Jiang JG, Rubin JL. Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV1. J Cyst Fibros. 2019 Jan;18(1):94-101. doi: 10.1016/j.jcf.2018.07.011. Epub 2018 Aug 23.
• Elborn JS, Ramsey BW, Boyle MP, Konstan MW, Huang X, Marigowda G, Waltz D, Wainwright CE; VX-809 TRAFFIC and TRANSPORT study groups. Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup: a pooled analysis. Lancet Respir Med. 2016 Aug;4(8):617-626. doi: 10.1016/S2213-2600(16)30121-7. Epub 2016 Jun 10.
• Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi: 10.1056/NEJMoa1409547. Epub 2015 May 17.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Ivacaftor	Other / unclassified	250 mg	Oral
Subject	Lumacaftor	Small molecule	400 mg	Oral
Subject	Lumacaftor	Small molecule	600 mg	Oral

Indications